The invention relates to a measuring device for examining a medium, especially one that is liquid or free-flowing, and a process for manufacturing a measuring device of this type.
From PCT publication WO 95/31716 a measuring device is already known which has an electrically conducting layer located on a substrate layer and having two layer areas each arranged in the plane of the layer and electrically insulated from each other. The two layer areas form electrodes which have approximately the shape of a comb. The layer areas mesh into each other with their comb structures. This previously known measurement device has proven valuable in practice, especially for the physiological examination of biological cells which are arranged in a nutrient medium and adhere during measurement to the surface of the substrate layer and the planar conducting layer areas located on it. With this previously known measurement device, on the one hand, conductivity measurements can be performed on a cell membrane area of the cells located in the deposit area of the cells, and on the other hand, the measurement device also makes possible a capacitive uncoupling of electric signals from the cell membrane.
A disadvantage of this previously known measurement device, however, still exists in that it only allows an examination of the cells on the conductive layer areas and the underside of the cells which is facing the substrate layer. It has been revealed, however, that biological cells can have different electric and/or optical properties in various areas of their cell membrane which, for example, can be brought forth by a locally varying diffusion of ions or proteins located in the cell liquid of the cells.
Therefore, an object of the invention is to create a measurement device, of the type described above, which allows for further examination of the medium. In addition, an object of the invention is to provide a process for manufacturing such a measuring device.
This object is achieved in that the measuring device has at least two electrically and/or optically conducting layers or layer areas made of a solid material and located on a substrate layer, wherein these layers or layer areas are electrically and/or optically insulated from each other, in that at least one of these layers or layer areas is arranged in a layer stack, which has several layers arranged on top of each other on the substrate layer, in that the layer stack has, on its side facing away from the substrate layer, a recess that adjoins the electrically and/or optically conducting layers or layer areas; and in that at least one layer located in the layer stack, which is electrically and/or optically conducting, or the at least one layer area located in the layer stack, which is electrically and/or optically conducting, is spaced at a distance from the bottom of the recess.
The measuring device thus has a layer stack with-a recess, adjoined by at least one electrically and/or optically conducting layer or one layer area of the layer stack, which is set off at a distance from the bottom of the recess by at least one additional layer. Thus, on the limiting wall of the recess, an electrically conducting and/or optically transparent wall area is produced, which is arranged at a distance from the bottom of the recess. In this way, it is possible to emit electrical and/or optical signals into the medium located in the recess, or to receive them from the medium, at a position spaced from the bottom of the recess. In a measuring device which is electrically conducting at the layer or layer area adjacent to the recess and spaced from the bottom of the recess, conductivity measurements or capacitive measurements, for example, can be carried out, for example in a direction transverse to the extension plane of the substrate layer or in a direction running parallel to it, on the medium located in the recess and/or particles contained in it, for example biological cells which have settled on the bottom of the recess.
In a measuring device in which the layer or layer area spaced from the bottom of the recess and adjacent to the recess is optically transparent, it is even possible to measure the optical transmission or emission in the medium in a direction running transversely to the extension plane of the substrate layer or in a direction parallel to it. A transmission measurement can occur, for example, such that through one of the optically transparent layers or layer areas, an optical radiation is coupled into the recess and transmitted through the medium to the other optically transparent layer, and via this layer it is uncoupled again from the recess. The measurement device thus allows a three-dimensional investigation of a medium located in the recess.
In an advantageous way, with the electrically and/or optically conducting layer, which is spaced from the bottom of the recess in the limiting wall of the recess and oriented with its active surface transverse to the coating plane of the substrate layer, a compactly designed measurement device is produced, which requires only a comparatively small area on the substrate layer. In a measuring device constructed as a semiconductor chip, expensive chip area can thus be saved.
In one advantageous embodiment of the invention, at least one layer of the layer stack has at least two electrically and/or optically conducting layer areas arranged next to each other in the coating plane of this layer, each being adjacent to the recess and insulated from each other electrically and/or optically. The medium located in the recess can then be examined optically and/or electrically at a distance from the bottom of the recess in the coating plane of this layer. It is even possible herein that the layer have more than two layer areas, each adjacent on the sides of the recess and electrically and/or optically conducting, so that the medium located in the recess can then be examined in different directions in the coating plane of this layer, depending on between which of these layer areas in the recess, an optical and/or electrical measuring path is formed.
It is especially advantageous if, on each side of an optically conducting layer or layer area, a metallic layer or layer area is arranged transverse to the coating plane as an optical reflection layer. Radiation losses in the layers adjacent to the optically conducting layer are thereby reduced. The metallic. layers adjacent to the optical layer can optionally be adjacent to the recess, so that these layers also allow coupling and/or uncoupling of electric signals into the optically conducting layer outside of a guide for the optical radiation.
In one especially advantageous embodiment of the invention, on the limiting wall of the recess, at least one electric and/or optically conducting layer area forms a projection relative to at least one layer area adjacent to it, and the layer area having the projection and the layer area adjacent to it are preferably arranged in different coating planes of the layer stack. In an electric layer a small ohmic contact resistance then occurs between the layer and the medium located in the recess, while in an optically conducting layer the projection allows a small optical radiation resistance between the layer and the medium.
In one advantageous embodiment of the invention, the limiting wall of the recess has at least one coupling location, which is located on an optically conducting layer and/or on an optically conducting layer area, for the targeted emission of optical radiation into the recess. In the limiting wall, lying opposite the coupling position in the emission direction of the radiation, at least one uncoupling position is arranged on an optically transparent layer or layer area. The coupling position and/or the uncoupling position is (are) arranged on a projection which projects into the recess beyond the layers on both sides adjacent to it and can be extended against the restoring force of its material from a rest position transverse to the coating plane of the layer having the projection. The measuring device then allows the measurement of dynamic pressure changes in the medium to be examined, which is located in the recess.
A dynamic pressure change in the medium, or a pressure wave that propagates transversely to the extension direction of the projection in the medium, causes an excursion of the projection having the coupling or uncoupling position from its resting position, such that the transmission path is, changed at the uncoupling position by optical radiation radiated into the medium at the coupling position. A dynamic pressure change in the medium thus leads to a change of the optical signal uncoupled from the medium at the uncoupling position, which can be detected by a corresponding optical sensor. This can be integrated in the layer stack and/or optically connected to the uncoupling-side, optically transparent layer or layer area.
An expedient embodiment of the invention has at least one sensor arranged in the bottom of the recess for examining the medium located in the recess. The sensor can be, for example, a field effect transistor for detecting ions contained in the medium, a sensor for measuring a gas content and/or an optical sensor. The medium located in the recess can then be even further examined. Thus, for example, using the sensor, measurements can be made on a cell in a nutrient medium, which is located in the recess and contains the biological cell that settles on the bottom of the recess.
It is advantageous if an ion-selective membrane is arranged in the recess that preferably grasps behind a projection of the limiting wall of the recess. The layers or layer areas located on the wall area covered by the membrane and/or a sensor optionally located in the bottom of the recess then makes possible a detection of certain ions contained in the medium and to which the membrane is permeable, while other ions or particles are kept away from these layers and/or layer areas and/or the sensor. With a membrane that grasps behind a projection of the limiting wall of the recess, an especially good adhesive force of the membrane results on the layer stack.
In another advantageous embodiment of the invention, the layer stack has several recesses, preferably having different dimensions and arranged in an array-shape, which each adjoin at least two electrically and/or optically conducting layers or layer areas. At least one of the layers or layer areas adjoining the respective recess is arranged at a distance from the bottom of the recess. The openings of the differently dimensioned recesses then form a mechanical filter for particles contained in the medium to be examined, so that with the measuring devices formed by the respective individual recesses and layers or layer areas adjoining them, particles having different sizes can be examined. In addition, the recesses of the individual measurement devices can have different volumes, so that depending on the quantity of the liquid or flee-flowing medium to be examined, a recess can be chosen with a volume that is fitted to the quantity of the medium.
In regard to the process for manufacturing a measuring device of the type mentioned at the outset, the above object is achieved by mounting layers on a substrate layer to form a layer stack having at least two electrically and/or optically conducting layers, between which at least one electrically and/or optically insulating intermediate layer is arranged. On the side of the layer stack facing away from the substrate layer, a recess is made in the layer stack, which penetrates the electrically and/or optically conducting layers and/or adjoins them on the side.
In addition to the already mentioned advantages of the measuring device, the process has the additional advantage that it can be integrated well into the manufacturing process for producing a semiconductor chip, in particular a CMOS-chip. The layers mounted on the substrate layer during the manufacture of the layer stack can additionally be used for the manufacture of other structures to be integrated into the semiconductor chip, for example strip conductors, transistors, and/or sensors, in which these layers are masked in a customary manner, for example using a photo-lithographic process. It is especially advantageous in the process that the recess is made in the layer stack only after the production of all layers necessary for the layer stack, i.e., the photo-resist layers necessary for the photolithographic manufacture of the additional structures of the semiconductor chip are each applied on the individually interconnected mounted layers of the layer stack before the recess is made in the layer stack. In this way, the recess cannot prevent the photo-resist, applied for example by a rotational molding process, from spreading out on the surface of the separate layers. Also, formation of tears, which can occur when a layer is applied onto an edge or a shoulder, is prevented by the subsequent creation of the recess in the layer stack.
The above object of the invention can also be achieved in terms of the process, wherein a substrate layer is provided with a layer stack by mounting at least one electrically and/or optically insulating first layer and at least one electrically and/or optically conducting second layer, such that on the side of the layer stack facing away from the substrate layer a recess adjoining the electrically and/or optically conducting second layer and/or penetrating through it is created in the layer stack, and such that on the bottom of the recess at least one electrically and/or optically conducting third layer is arranged spaced from the second layer.
This process also allows the manufacture of a three-dimensional measuring device having a layer that is spaced from the bottom of the recess and that is electrically and/or optically conducting. In addition, however, the bottom of the recess is itself also electrically and/or optically conducting and can also be used to examine a medium located in the recess. The process can be integrated well into the manufacturing process for a semiconductor chip.
Finally, the above object can be achieved in terms of the process, wherein a layer stack is provided on a substrate layer by creating at least one electrically and/or optically insulating layer and at least one electrically and/or optically conducting layer; the electrically and/or optically conducting layer is subdivided into at least two electrically and/or optically conducting layer areas, which are electrically and/or optically insulated from each other; and a recess that penetrates and/or adjoins the electrically and/or optically conducting layer areas is made in the layer stack on the side of the layer stack facing away from the substrate layer, so that the bottom of the recess is spaced from the electrically and/or optically conducting layer areas. This process has the advantage that the measuring device manufactured thereby allows an examination of the medium located in the recess in the plane of the electrically and/or optically conducting layer that contains the layer areas.
In an especially advantageous embodiment of the process, an indentation relative to an adjacent electrically and/or optically conducting layer or layer area is formed by removing layer material on the limiting wall of the recess in the region of an electrically and/or optically insulating layer or layer area. In an electrically conducting layer or layer area a small transition resistance results between the layer or the layer area and the medium to be examined which is located in the recess. Electric signals can be better coupled and/or uncoupled into or out of the medium in this way. Correspondingly, the indentation in an optically conducting layer or layer area allows a small optical transition resistance between the layer or the layer area and the medium.
In an especially advantageous embodiment of the process, the layer stack is brought into contact with an etchant in order to create the recess, and the layer materials of the individual layers or layer areas are selected in such a way, in order to form the indentation in the limiting wall of the recess, that they have different etching rates with regard to the etchant. The limiting wall of the recess can be provided with indentations or a layered profiling in a simple way.
It is advantageous if the substrate is provided with a layer stack having, transverse to the coating plane of its layers, a metallic layer as an optical reflection layer on both sides of an optically conducting layer or layer area. The metallic layers function then, on the one hand, as an optical reflection layer and can, on the other hand, also be used to couple electric signals into and/or uncouple electric signals from the medium.